In the nutritional pathology of liver disease, with regard to the carbohydrate metabolism, abnormal glucose tolerance is frequently observed generally due to changes in glycolytic enzyme activity and reduced insulin sensitivity at the periphery. This is especially the case in liver cirrhosis, where energy consumption is enhanced and the availability of carbohydrates as an energy substrate is decreased. Observations of the protein metabolism in hepatitis and liver cirrhosis show an imbalance of plasma amino acids (a decrease in the branched chain amino acid/aromatic amino acid ratio (the Fischer ratio)), enhanced protein catabolism, hyperammonemia, and hypoproteinemia due to a negative nitrogen balance. Furthermore, with regard to the lipid metabolism a decrease in polysaturated fatty acids and lipid-soluble vitamins is seen.
Liver cirrhosis includes compensated and decompensated cirrhosis, which differ in pathology as well as in their metabolic and nutritional management. Compensated cirrhosis can be managed in much the same way as chronic hepatitis. However, decompensated cirrhosis is a state of chronic liver failure, and since protein catabolism is enhanced, excess protein administration may lead to hyperammonemia. Oral administration of the branched chain amino acids (BCAAS) valine, leucine, and isoleucine can suppress protein catabolism in peripheral tissues, and enhance protein synthesis in the liver. Furthermore, BCAAs metabolized in muscles form alanine, which activates glucogenesis (the glucose-alanine cycle) in the liver, and improves the efficiency of carbohydrates as an energy substrate. Therefore, PCAA preparations (Hepan ED®, Aminoleban EN®: 50 to 150 g/day) are used to supplement a lack of energy in skeletal muscles.
On the other hand, when a living body experiences something excessively invasive such as surgery, infection, or scalds, the production of local and systemic inflammatory mediators is enhanced. Cytokines in particular are important mediators, inducing a variety of reactions in the circulatory, endocrine, immune and metabolic systems, etc.
In general, metabolic reactions during invasion characteristically include enhanced proteolysis of body proteins, especially skeletal muscles; production of glycerol and fatty acids due to enhanced lipolysis; and gluconeogenesis, acute-phase protein production and albumin production in the liver. Both cellular and humoral immunity may be suppressed during invasion, and immune-related protein synthesis is expected to decrease as protein catabolism is considerably enhanced.
The involvement of various cytokines in metabolic changes in invaded bodies has been revealed in experiments where cytokines themselves are administered, experiments that block the production or action of cytokines, etc. Specifically, the metabolic variations caused by TNF-α, IL-1, and IL-6 are: (1) enhanced glycogenolysis, hyperglycemia and hypoglycemia with regard to the glucose metabolism, (for example, Meszaros K et al. “Tumor necrosis factor increases in vivo glucose utilization of macrophage-rich tissues” Biochem. Biophys. Res. Commun., Vol. 149, No. 1: pp. 1-6, 1987 Nov. 30; Tracey, K J et al. “Shock and tissue injury induced by recombinant human cachectin” Science, Vol. 234, No. 4775: pp. 470-474, 1986 October 24; Fukushima, R et al. “Different roles of IL-1 and TNF on hemodynamics and interorgan amino acid metabolism in awake dogs” Am. J. Physiol., Vol. 262, No. 3, Pt. 1: pp. E275-E281, 1992 March), (2) increased muscular decay and amino acid release, increased intestinal glutamine uptake, increased intestinal alanine release, increased hepatic amino acid uptake, and enhanced acute-phase protein synthesis with regard to the amino acid and protein metabolism, (for example, Fukushima, R et al. “Different roles of IL-1 and TNF on hemodynamics and interorgan amino acid metabolism in awake dogs” Am. J. Physiol., Vol. 262, No. 3, Pt. 1: pp. E275-E281, 1992 March; Moldawer, L L et al. “Interleukin 1 and tumor necrosis factor do not regulate protein balance in skeletal muscle” Am. J. Physiol., Vol. 253, No. 6, Pt. 1: pp. C766-C773, 1987 December), and (3) enhanced fatty acid degradation and decreased lipoprotein lipase activity with regard to the lipid metabolism (for example, Feingold, K R et al. “Multiple cytokines stimulate hepatic lipid synthesis in vivo” Endocrinology, Vol. 125, No. 1: pp. 267-274, 1989 July; Grunfeld, C et al. “Tumor necrosis factor: immunologic, antitumor, metabolic, and cardiovascular activities” Adv. Intern. Med., Vol. 35: pp. 45-71, 1990; Feingold, K R et al. “Tumor necrosis factor stimulates hepatic lipid synthesis and secretion” Endocrinology, Vol. 124, No. 5: pp. 2336-2342, 1989 May).
A rational way to prevent the metabolic abnormalities and organ damage caused by cytokines during invasion would be to cause normal cytokine production locally, whilst preventing cytokine spread to the whole body. Such methods include the use of enteral nutrition, ω-3 fatty acids, or growth hormones.
There are several reports regarding differences in cytokine production due to differences in nutrition administration routes during invasive stress. In healthy adults who are not experiencing invasive stress, administration of enteral or intravenous nutrition for one week does not cause any obvious differences in blood TNF-α and IL-6 levels (for example, Lowry, S F et al. “Nutrient modification of inflammatory mediator production” New Horiz., Vol. 2, No. 2: pp. 164-174, 1994 May). However, when administration of enteral or intravenous nutrition continues for seven days and is followed by intravenous injection of endotoxins, systemic reactions, including fever and release of TNF-α and stressor hormones, are reported to be milder for enteral nutrition than for intravenous nutrition (for example, Fong, Y M et al. “Total parenteral nutrition and bowel rest modify the metabolic response to endotoxin in humans” Ann. Surgery., Vol. 210, No. 4: pp. 455-457, 1989 October).